Adjunctive Testing in the Evaluation of Adults After Kawasaki Disease

Daniels, Lori B.; Burns, Jane C.

doi:10.1253/circj.cj-15-0996

Cited by 3 publications

(2 citation statements)

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“…In addition to vascular fibrosis, KD patients can also develop myocardial fibrosis (18,19). It has recently been reported that convalescent KD patients with low cardiac ejection fractions due to myocarditis show a sustained elevation of serum fibrotic biomarkers (20).…”

Section: Introductionmentioning

confidence: 99%

“…It has recently been reported that convalescent KD patients with low cardiac ejection fractions due to myocarditis show a sustained elevation of serum fibrotic biomarkers (20). Therefore, it has been suggested that a subset of KD patients with acute, severe myocarditis may be at risk of developing chronic interstitial fibrosis, which results in a progressive decline in cardiac function (19,20).…”

Section: Introductionmentioning

confidence: 99%

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Mechanistic Target of Rapamycin Inhibition Prevents Coronary Artery Remodeling in a Murine Model of Kawasaki Disease

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Parsons

D'Silva

et al. 2022

Arthritis & Rheumatology

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Objective Remodeling of the coronary arteries is a common feature in severe cases of Kawasaki disease (KD). This pathology is driven by the dysregulated proliferation of vascular fibroblasts, which can lead to coronary artery aneurysms, stenosis, and myocardial ischemia. We undertook this study to investigate whether inhibiting fibroblast proliferation might be an effective therapeutic strategy to prevent coronary artery remodeling in KD. Method We used a murine model of KD (induced by the injection of the Candida albicans water‐soluble complex [CAWS]) and analyzed patient samples to evaluate potential antifibrotic therapies for KD. Results We identified the mechanistic target of rapamycin (mTOR) pathway as a potential therapeutic target in KD. The mTOR inhibitor rapamycin potently inhibited cardiac fibroblast proliferation in vitro, and vascular fibroblasts up‐regulated mTOR kinase signaling in vivo in the CAWS mouse model of KD. We evaluated the in vivo efficacy of mTOR inhibition and found that the therapeutic administration of rapamycin reduced vascular fibrosis and intimal hyperplasia of the coronary arteries in CAWS‐injected mice. Furthermore, the analysis of cardiac tissue from KD fatalities revealed that vascular fibroblasts localizing with inflamed coronary arteries up‐regulate mTOR signaling, confirming that the mTOR pathway is active in human KD. Conclusion Our findings demonstrate that mTOR signaling contributes to coronary artery remodeling in KD, and that targeting this pathway offers a potential therapeutic strategy to prevent or restrict this pathology in high‐risk KD patients.

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Section: Introductionmentioning

confidence: 99%